Pharmacologic blockade of vascular adhesion protein-1 lessens neurologic dysfunction in rats subjected to subarachnoid hemorrhage

Xu, Hao; Garcia, Maggie; Testai, Fernando D.; Vetri, Francesco; Barabanova, Alexandra; Pelligrino, Dale A.; Paisansathan, Chanannait

doi:10.1016/j.brainres.2014.08.036

Cited by 28 publications

(29 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Male Sprague-Dawley rats were used in this study, which was approved by the University of Illinois Institutional Animal Care and Use Committee.We utilized the endovascular perforation model of SAH as previously described [16,17]. Briefly, rats (250-300 g in body weight) were anesthetized with 70% N 2 O/30% O 2 /2% isoflurane through intubation.…”

Section: Methodsmentioning

confidence: 99%

“…The placement of the cranial window was performed as previously described [16,17]. Briefly, 48 h after SAH, animals were reanesthetized with isoflurane, and paralyzed with curare (1 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

“…Pial arteriole function was assessed as previously described [16,17]. Basically, surface arterioles (diameter: 25-45 µm) in the somatosensory cortex (approx.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

The Role of HMGB1 in Pial Arteriole Dilating Reactivity following Subarachnoid Hemorrhage in Rats

Changyaleket

Vályi-Nagy³

et al. 2016

J Vasc Res

Self Cite

View full text Add to dashboard Cite

High-mobility group box 1 protein (HMGB1) has been implicated in inflammatory responses, and is also associated with cerebral vasospasm after subarachnoid hemorrhage (SAH). However, there are no direct evident links between HMGB1 and cerebral vasospasm. We therefore investigated the effects of HMGB1 on pial arteriole reactivity following SAH in rats. We initially found that SAH induced a significant decrease in pial arteriole dilating responses to sciatic nerve stimulation (SNS), hypercapnia (CO₂), and the topical suffusion of acetylcholine (ACh), adenosine (ADO), and s-nitroso-N-acetylpenicillamine (SNAP) over a 7-day period after SAH. The percent change of arteriolar diameter was decreased to the lowest point at 48 h after SAH, in response to dilating stimuli (i.e., it decreased from 41.0 ± 19.0% in the sham group to 11.00 ± 0.70% after SNS) (n = 5, p < 0.01). HMGB1 infusion in the lateral ventricle in normal rats for 48 h did not change the pial arteriole dilating response. In addition, inhibitors of HMGB1-receptor for advanced glycation end-product or HMGB1-toll-like receptor 2/4 interaction, or the HMBG1 antagonist did not improve pial arteriole reactivity 48 h after SAH. These findings suggest that HMGB1 may not be a major player in cerebral vascular dilating dysfunction after SAH.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Role of HMGB1 in Pial Arteriole Dilating Reactivity following Subarachnoid Hemorrhage in Rats

Changyaleket

Vályi-Nagy³

et al. 2016

J Vasc Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…The details of SAH endovascular perforation model were previously described [33]. Briefly, rats weighing 250–300 g were anesthetized with 70% N 2 O/30% O 2 /2% isoflurane using a rodent ventilator.…”

Section: Methodsmentioning

confidence: 99%

“…After completion of the surgery, the anesthesia with isoflurane was switched to fentanyl infusion for monitoring of rhodamine-6G (R6G)-labeled leukocyte. This semiquantitative method of in vivo assessment of leukocyte trafficking has been described in details in our previous publications [33, 37]. Briefly, loading dose of R6G (0.2 mg) was applied intravenously, followed by 0.2 mg/h maintenance dose.…”

Section: Methodsmentioning

confidence: 99%

Heparanase promotes neuroinflammatory response during subarachnoid hemorrhage in rats

Changyaleket

Chong

Dull

et al. 2017

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundHeparanase, a mammalian endo-β-D-glucoronidase that specifically degrades heparan sulfate, has been implicated in inflammation and ischemic stroke. However, the role of heparanase in neuroinflammatory response in subarachnoid hemorrhage (SAH) has not yet been investigated. This study was designed to examine the association between heparanase expression and neuroinflammation during subarachnoid hemorrhage.MethodsRats were subjected to SAH by endovascular perforation, and the expression of heparanase was determined by Western blot analysis and immunofluorescence in the ipsilateral brain cortex at 24 h post-SAH. Pial venule leukocyte trafficking was monitored by using intravital microscopy through cranial window.ResultsOur results indicated that, compared to their sham-surgical controls, the rats subjected to SAH showed marked elevation of heparanase expression in the ipsilateral brain cortex. The SAH-induced elevation of heparanase was accompanied by increased leukocyte trafficking in pial venules and significant neurological deficiency. Intracerebroventricular application of a selective heparanase inhibitor, OGT2115, which was initiated at 3 h after SAH, significantly suppressed the leukocyte trafficking and improved the neurological function.ConclusionsOur findings indicate that heparanase plays an important role in mediating the neuroinflammatory response after SAH and contributes to SAH-related neurological deficits and early brain injury following SAH.

show abstract

Vascular adhesion protein-1 defines a unique subpopulation of human hematopoietic stem cells and regulates their proliferation

Iftakhar-E-Khuda

Pessia

Zheng

et al. 2021

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Although the development of hematopoietic stem cells (HSC) has been studied in great detail, their heterogeneity and relationships to different cell lineages remain incompletely understood. Moreover, the role of Vascular Adhesion Protein-1 in bone marrow hematopoiesis has remained unknown. Here we show that VAP-1, an adhesin and a primary amine oxidase producing hydrogen peroxide, is expressed on a subset of human HSC and bone marrow vasculature forming a hematogenic niche. Bulk and single-cell RNAseq analyses reveal that VAP-1+ HSC represent a transcriptionally unique small subset of differentiated and proliferating HSC, while VAP-1− HSC are the most primitive HSC. VAP-1 generated hydrogen peroxide acts via the p53 signaling pathway to regulate HSC proliferation. HSC expansion and differentiation into colony-forming units are enhanced by inhibition of VAP-1. Contribution of VAP-1 to HSC proliferation was confirmed with mice deficient of VAP-1, mice expressing mutated VAP-1 and using an enzyme inhibitor. In conclusion, VAP-1 expression allows the characterization and prospective isolation of a new subset of human HSC. Since VAP-1 serves as a check point-like inhibitor in HSC differentiation, the use of VAP-1 inhibitors enables the expansion of HSC.

show abstract

Pharmacologic blockade of vascular adhesion protein-1 lessens neurologic dysfunction in rats subjected to subarachnoid hemorrhage

Cited by 28 publications

References 20 publications

The Role of HMGB1 in Pial Arteriole Dilating Reactivity following Subarachnoid Hemorrhage in Rats

The Role of HMGB1 in Pial Arteriole Dilating Reactivity following Subarachnoid Hemorrhage in Rats

Heparanase promotes neuroinflammatory response during subarachnoid hemorrhage in rats

Vascular adhesion protein-1 defines a unique subpopulation of human hematopoietic stem cells and regulates their proliferation

Contact Info

Product

Resources

About